BMB-4 MiR-718 Impacts H4 modifications Involved in Cancer

Abstract

In this study we have been researching the effects of a microRNA, miR-718, on histone 4 modifications that are related to Autism Spectrum Disorders (ASD). ASD is a neurodevelopmental disorder that affects speech, repetitive behavior, and social interactions. It has been suggested that ASD patients experience an increase in expression of miR-718 due to an increase in the IRAK1 gene, which shares an overlapping transcript with miR-718. Though the miR-718 to ASD relationship is not confirmed, we have empirically shown that an increase in miR-718's expression directly decreases the expression of miR-132, which is a microRNA known to be related to ASD. MiR-718 and miR-132 collectively target 10 genes that effect the modifications of histones in the nucleus. Since increases in Histone 4 lysine 20 methylation (H4K20me1) may be related to ASD, we hypothesized that increasing the expression of miR-718 will subsequently increase the occurrence of H4K20me1. To test this, human neuronal cells (SH-SY5Y), were grown and treated with an siRNA that mimics miR-718 or a control/scramble siRNA. RNA and histones were isolated from these cells for analysis. The RNA isolated was used in a RT-qPCR assay to quantify the amount of miR-718 in both the control group and the treatment group. Histones were examined using a histone 4 modification array ELISA-based assay. Although there was no significant change in H4K20me1, we found that an increase in miR-718's expression led to a significant decrease in both H4R3me2A (p=0.033) and H4R3me2S (p=0.049). In conclusion, the histones that were significantly decreased, H4R3me2A and H4R3me2S, were seen in studies involved in colorectal cancer, so further research into miR-718’s effects on H4 modifications may be more cancer-related.

Keywords

microRNA, epigenetics, histones, cancer

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Apr 12th, 9:30 AM Apr 12th, 11:30 AM

BMB-4 MiR-718 Impacts H4 modifications Involved in Cancer

University Readiness Center Greatroom

In this study we have been researching the effects of a microRNA, miR-718, on histone 4 modifications that are related to Autism Spectrum Disorders (ASD). ASD is a neurodevelopmental disorder that affects speech, repetitive behavior, and social interactions. It has been suggested that ASD patients experience an increase in expression of miR-718 due to an increase in the IRAK1 gene, which shares an overlapping transcript with miR-718. Though the miR-718 to ASD relationship is not confirmed, we have empirically shown that an increase in miR-718's expression directly decreases the expression of miR-132, which is a microRNA known to be related to ASD. MiR-718 and miR-132 collectively target 10 genes that effect the modifications of histones in the nucleus. Since increases in Histone 4 lysine 20 methylation (H4K20me1) may be related to ASD, we hypothesized that increasing the expression of miR-718 will subsequently increase the occurrence of H4K20me1. To test this, human neuronal cells (SH-SY5Y), were grown and treated with an siRNA that mimics miR-718 or a control/scramble siRNA. RNA and histones were isolated from these cells for analysis. The RNA isolated was used in a RT-qPCR assay to quantify the amount of miR-718 in both the control group and the treatment group. Histones were examined using a histone 4 modification array ELISA-based assay. Although there was no significant change in H4K20me1, we found that an increase in miR-718's expression led to a significant decrease in both H4R3me2A (p=0.033) and H4R3me2S (p=0.049). In conclusion, the histones that were significantly decreased, H4R3me2A and H4R3me2S, were seen in studies involved in colorectal cancer, so further research into miR-718’s effects on H4 modifications may be more cancer-related.